Pain is a multidimensional experience that involves sensory, cognitive and affective mechanisms. The constellation of interactions between these factors makes the treatment of clinical pain challenging and often a financial burden. Mindfulness meditation has been found to significantly improve pain symptoms in experimental and clinical settings, but lack of mechanistic data has limited clinical deployment of this cost- effective and narcotic-free treatment. Recent findings from our laboratory determined that meditation, after only four days (20 minutes/day) of training, reduced pain intensity by 40% and pain unpleasantness ratings by 57%. Employing an emerging MRI technique (arterial spin labeling), we found that meditation-related pain relief was associated reduced pain-related brain activity in the primary somatosensory cortex and increased activity in brain regions such as the anterior insula, anterior cingulate cortex, and orbitofrontal cortex. These latter regions are involved in cognitive control, emotion regulation, and executive processing. These findings demonstrate that meditation engages multiple brain mechanisms during pain relief. However, the contribution of other cognitive factors such as expectations, facilitator attention, anxiety reduction, and conditioning /extinction processes remains poorly understood. Such factors are critically involved in the placebo effect. Accordingly, the proposed study seeks to determine if meditation-related pain relief engages brain mechanisms that are distinct from those of placebo analgesia. Functional imaging methodologies will be employed to assess brain activation during mediation-induced pain relief and during conditioned placebo analgesia. The proposed investigation will provide significant insights into the neural substrates involved in the modulatin of pain by cognitive factors.